Gene Delivery Using Physical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 102

Figure 3.4 Effect of ultrasound on breaking pattern of lipid and polymeric microbubbles for
gene delivery.
on cell lines or different anatomic locations in the human body, which has been con-
firmed with its diagnostic applications. Thus, ultrasound-mediated gene delivery,
which is a comparatively safe technique, is an effective alternative to the viral mode
of gene delivery for the treatment of various body disorders, including respiratory
disorders, the most complicated to treat. The ultrasound technique has shown to cre-
ate membrane pores and facilitates intracellular gene transfer through passive diffu-
sion of the gene across membrane pores [210,215] . Consequently, the size, form, and
local concentration of plasmid DNA play a very significant role in determining the
transfection efficiency in the cell lines, as well as in vivo conditions. Reducing DNA
size, either by methods of standard molecular biology or through proper formulation
by condensing it, could result in further improvement in transfection efficiency. This
concept of condensing the DNA with cationic lipids, thereby reducing its size and
enhancing its stability against cytoplasmic nucleases, was used by Rainov et al. and
Proctor et al. for significantly enhanced DNA transfection in cell culture and in vivo
[215,216] .
Ultrasound exposure in the presence of microbubble echo-contrast agents [217]
has shown significantly enhanced acoustic cavitations with enhanced transgene
expression in vascular cells compared with naked DNA transfection alone [218] . The
ultrasound contrast agent (Albunex), which consists of elastic and compressible gas-
filled microbubbles, has also been successfully used to improve ultrasound-mediated
transgene expression [219] . These echo-contrast agents lower the transfection thresh-
old by acting as cavitation nuclei [220,221] and enhance the energy transfer for more
cell permeabilization. The microbubble explosion and energy transfer may form
localized jets that may act like a random array of microneedles, opening pathways
through the cell membrane [222] . Current ultrasound-mediated gene therapy is using